"Bexxar is an NHL treatment that is tailored to administer a targeted and patient-specific therapeutic dose of radiation, thereby preventing either under or overdosing of radiation. For patients who have not responded or have relapsed following front line treatments, Bexxar is an important and welcome option."

By GlaxoSmithKline Inc., [RxPG] Health Canada has approved a new treatment that could offer hope for those who suffer from what is considered an incurable form of non-Hodgkin's lymphoma (NHL) and who have failed on, or relapsed following, other treatments. Health Canada approved Bexxar(TM) (tositumomab and iodine I 131 tositumomab) therapy for the treatment of patients with CD20 positive relapsed or refractory, low grade, follicular, or transformed non-Hodgkin's lymphoma, including patients with rituximab- refractory NHL.

"Bexxar represents an important new direction in cancer therapy," says Dr. Harold J. Olney, hematologist, medical oncologist and principal investigator for Bexxar's current Canadian clinical trial. "Bexxar is an NHL treatment that is tailored to administer a targeted and patient-specific therapeutic dose of radiation, thereby preventing either under or overdosing of radiation. For patients who have not responded or have relapsed following front line treatments, Bexxar is an important and welcome option."

Bexxar is the latest of a new generation of patient-tailored cancer treatments that specifically targets non-Hodgkin's lymphoma cells, while minimizing risk to surrounding healthy cells. Bexxar is given at a dose specific to individual patient characteristics, usually in an outpatient setting. Administered in a short treatment course, Bexxar can provide long- lasting responses in patients whose disease has not responded to other treatments. In clinical studies, approximately one in four patients on Bexxar were shown to have a durable complete response of greater than one year.

Bexxar was granted Health Canada's Priority Review status, which is reserved for new drugs that have the potential ability to address serious, life-threatening or severely debilitating illness or conditions for which there is an unmet medical need. Bexxar is expected to be available in Canada in October, 2005.

About Bexxar Therapy

Bexxar is a dual-action therapy that pairs the tumor-targeting ability of a cytotoxic (cancer killing) monoclonal antibody (tositumomab) and the therapeutic effect of patient-specific radiation (iodine-131) dosing. Antibodies (tositumomab) target and attach to cancer cells deep inside the tumor (antigen CD20 found on NHL cells). The radiation dose (iodine 131) then targets tumors with minimal risk to surrounding healthy cells.

Clinical Study Results

The efficacy of Bexxar therapy was examined in a multi-center, single-arm study of 40 patients with follicular NHL whose disease had relapsed following or had not responded to rituximab. The median age of patients in the study was 57 (range: 35-78) and the median number of prior chemotherapies was four (range: 1-11). Eighty-eight per cent of patients met the definition of rituximab refractory (defined as no response or a response of less than six months in duration). In these patients with rituximab refractory disease, 63 per cent of patients had a response to Bexxar, with a median duration of response of 25 months. Twenty-nine per cent of these patients had a complete response (no clinical signs of disease) to Bexxar. The median duration of complete responses had not been reached after a median follow up of 26 months.

The results of this study were supported by demonstration of durable objective responses (lasting more than one year) in one phase III and three other single-arm studies, enrolling 190 patients with rituximab-naive, follicular NHL, with or without transformation, who had relapsed following or were refractory to chemotherapy. In these studies, the overall response rates ranged from 47 per cent to 64 per cent and the median durations of response ranged from 12 to 18 months.

Side Effects

The most common adverse reactions occurring in the clinical trials included neutropenia, thrombocytopenia and anemia. Less common but severe reactions included pneumonia, pleural effusion and dehydration.

The most common non-hematologic side effects included asthenia (weakness), fever, nausea, infection and cough. Bexxar was associated with a risk of hypothyroidism and human anti-murine antibody (HAMA) formation. Certain chemotherapy agents and ionizing radiation have been associated with the development of myelodysplasia (MDS), secondary leukemia and solid tumors. MDS, secondary leukemia and solid tumors have also been observed in patients receiving Bexxar therapy.

Administration of Bexxar may result in infusion-related reactions that may be induced by the administration of foreign proteins. Hypersensitivity reactions occurred in six per cent of patients. Adjustments of the rate of infusion to control adverse reactions were required in seven per cent of patients.

Bexxar Therapy

Bexxar consists of four components administered in two steps over seven to fourteen days, usually on an outpatient basis. The first set of infusions includes the non-radioactive antibody, tositumomab, used to improve the distribution in the body of the subsequent radioactive antibody and increase its uptake in the tumor, followed by a dosimetric infusion, containing the antibody and a trace amount of radioactive iodine 131. This dosimetric step allows for visualization of the location of the radioisotope and the determination of the rate of clearance of radioactivity from the body by the use of gamma camera counts obtained at three time points. Clearance is dependent on factors such as tumor size and bone marrow involvement. From these determinations, the patient-specific amount of radioactivity necessary to deliver the targeted therapeutic total body dose of radiation can be calculated. Seven to fourteen days after the dosimetric step, the patient returns for the therapeutic step, which again includes two infusions, beginning with the non-radioactive antibody, but this time followed by the calculated patient-specific radioactivity needed to deliver the targeted total body dose of radiation.

About non-Hodgkin's Lymphoma

Non-Hodgkin's lymphoma is a form of cancer that affects the blood, bone marrow and lymphatic tissues. Unlike most major forms of cancer, both incidence and mortality rates of NHL are increasing. Incidence rates for NHL in Canada have more than doubled over the last thirty years and are among the highest in the world.(1) The Canadian Cancer Society estimates that 6,400 new cases will be diagnosed in 2005 and that 3,000 Canadians will die this year from the disease(2). Transformed non-Hodgkin's lymphoma can be an aggressive and difficult to treat form of follicular non-Hodgkin's lymphoma with a particularly poor prognosis.

GlaxoSmithKline Inc. -- one of the world's leading research-based pharmaceutical and health-care companies -- is committed to improving the quality of human life by enabling people to do more, feel better and live longer. In Canada, GlaxoSmithKline is a top 20 investor in research and development, contributing more than $130 million annually. GSK is an Imagine Caring Company, and is recognized as one of the 50 best companies to work for in Canada.